title: Gaucher disease: a diagnostic challenge for internists.
abstract: Gaucher disease (GD), the most common inherited lysosomal storage disorder, is a multiorgan disease due to an autosomal recessive defect of the gene encoding glucocerebrosidase enzyme, responsible for the accumulation of glucosylceramide (glucocerebroside) into reticuloendothelial cells, particularly in the liver, spleen and bone marrow. GD is a clinically heterogeneous disorder and it is conventionally classified in type 1 (non-neuronopathic disease), types 2 and 3 (acute and chronic neuronopathic disease, respectively). Features of clinical presentation and organ involvement as well as age, at presentation are highly variable among affected patients. Splenomegaly and/or thrombocytopenia are the most common presenting features either as incidental findings during routine blood count or physical examination. Other possible clinical manifestations can be hepatomegaly with abnormal liver function tests, bone pain often associated with skeletal complications (pathological fractures, avascular necrosis, osteopenia), pulmonary hypertension and, in neuronopathic forms, neurological manifestations (dysfunction of eye motility, mild mental retardation, behavioural difficulties, choreoathetosis and cramp attacks). For all these reasons GD diagnosis is often a real challenge for internists. In the presence of clinical suspicion of GD, the diagnosis has to be confirmed measuring the betaglucocerebrosidase activity in the peripheral leukocytes and by molecular analysis. Each patient needs an accurate initial multisystemic assessment, staging the damage of all the possible organs involved, and the burden of the disease, followed by regular followup. The correct and early diagnosis permits to treat patients properly, avoiding the complications of the disease.
authors.affiliation: Rare Diseases Center, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy. Electronic address: elena.cassinerio@virgilio.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Cassinerio
authors.affiliation: Rare Diseases Center, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Graziadei
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Poggiali
mesh_terms: D042241:Early Diagnosis; D061345:Early Medical Intervention; D005776:Gaucher Disease / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D007388:Internal Medicine / Q000379:methods
keywords: Chitotriosidase; Gaucher disease; Glucocerebroside; Lysosomial disorders; Rare diseases